Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.
 ...
PMID:Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. 1066 1

Endocrine disturbances, notably diabetes, have been well described as a complication of iron overload due to hereditary hemochromatosis and beta-thalassemia. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has also been well documented. The pattern of iron loading in African iron overload with saturated transferrin is similar to that seen in hereditary hemochromatosis. In addition, many symptoms ascribed to pituitary dysfunction are common to both conditions. The present study was undertaken to assess whether a similar pattern of endocrine dysfunction occurs in African iron overload. Thirty subjects with African iron overload and transferrin saturation >50%, plus 30 age and sex matched normal controls were studied. An iron profile, fasting plasma glucose, cortisol, DHEA-S, LH, FSH, growth hormone, prolactin, TSH, and FT4 levels were measured in all 60 subjects as well as testosterone in the males and estradiol in the females. Iron loading in the subjects with increased transferrin saturation ranged from moderate to severe. No significant differences were found in the mean testosterone, estradiol, LH, DHEA-S, growth hormone, prolactin, or TSH levels between the subjects and normal controls. In female subjects, although within the normal range, the mean FSH level was significantly higher, probably due to their being somewhat older and in a more advanced stage of menopause than the control females. Mean cortisol concentrations were increased in both genders in the patient group, significantly so in the females; however, values were within the reference range. We conclude therefore that there appears to be no major impairment of endocrine function in the basal state in African iron overload subjects with moderate to severe degrees of iron loading.
 ...
PMID:Basal endocrine status in African dietary iron overload. 1451 8

Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone (GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in dosages ranging from 0.5-1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical monitoring should be preformed on these patients while they are treated with GH.
 ...
PMID:Growth of children with beta-thalassemia major. 1575 40

A large number of children treated from the time of diagnosis with modern transfusion and chelation therapy are now entering early adolescence or early adulthood, and only now can we evaluate how many complications, secondary to iron overload, can be prevented by daily s.c. desferrioxamine (DFX) therapy. In 1989, we planned a multi-centre study on growth and endocrine complications in patients who started chelation therapy with DFX early in life. Height, weight, endocrine complications, haematological variables and compliance with DFX were evaluated in a study group of 238 patients aged 2-17 years with beta-thalassaemia major regularly followed in 13 paediatric and haematological Italian centres. The LMS method by Cole and Green and the Mann-Whitney test were applied for statistical analysis. Twenty-six patients with thalassaemia (12.4%) had growth hormone insufficiency, five patients (2.1%) had primary hypothyroidism and four patients (1.7%) had hypoparathyroidism. Delayed puberty was present in 18.4% of boys and 17.7% of girls. At the beginning of chelation, standing height was in the normal range when compared to Swiss standards, while in the following years a progressive decline of growth was observed in both sexes. In conclusion, our study noted a positive effect of DFX therapy on sexual maturation and endocrine complications. Nevertheless, short stature has persisted despite major advances in treatment.
 ...
PMID:Impact of long-term iron chelation therapy on growth and endocrine functions in thalassaemia. 1675 31

While hypertransfusion and subcutaneous iron chelation therapy have increased longevity of patients with beta-thalassemia (thal) major, endocrinopathies have become more common and impair the quality of their lives. Additionally, subcutaneous iron chelation therapy is an uncomfortable experience and can prevent patients from regular compliance with iron chelation therapy. We compared the efficacy of oral deferiprone (L1) to subcutaneous desferrioxamine (DFO) chelation therapy for the prevention of major endocrinopathies (growth hormone insufficiency, diabetes mellitus and gonadal dysfunction) among patients with beta-thal major to see if we could offer these patients an easier and more painless way to reduce their body iron load and related endocrine complications.
 ...
PMID:Comparison of oral and subcutaneous iron chelation therapies in the prevention of major endocrinopathies in beta-thalassemia major patients. 1679 51

Reduced serum insulin-like growth factor-1 (IGF-1) and hypogonadotrophic hypogonadism are common features of adult beta-thalassemia, and warrant evaluation of the growth hormone (GH)-IGF-1 axis. The aim of this study was to determine GH reserve in beta-thalassemia patients (9 females, 7 males, 15 major, 1 intermedia), age 29.3 +/- 6.9 years, BMI 21.3 +/- 1.9 kg/m2, and in 20 age, sex and BMI-matched healthy controls, using the GH-releasing hormone (GHRH)-arginine test. The associations between peak GH response and hormonal and biochemical indices were evaluated. Using BMI-related cut-off limits for peak GH response in the GHRH-arginine test, 4/16 beta-thalassemia patients had peak GH lower than 11.5 microg/l, the cut-off limit suggested for lean subjects, and were diagnosed as GH deficient (GHD). Using 9 microg/l as the cut-off limit 2/16 patients were GHD. Reduced serum IGF-1 and IGFBP-3 were present in 69% and 19% of the patients, respectively. Peak GH did not correlate with serum IGF-1, TSH, and fT4 levels or gonadal status. Neither peak GH nor IGF-1 correlated with serum ferritin. Our findings suggest that GHD is present in up to a quarter of adult beta-thalassemia patients. The clinical benefits of GH therapy need to be determined. GHD alone does not account for the high prevalence of reduced IGF-1 in adult beta-thalassemia.
 ...
PMID:Growth hormone reserve in adult beta thalassemia patients. 1770 95

The aetiology of the growth retardation occurring in patients with beta-thalassaemia major is considered to be multifactorial. Although growth hormone (GH) secretion appears to be normal in many thalassaemic patients with short stature, there is evidence indicating impaired GH secretion in approximately 3% of patients. The response to recombinant human GH treatment (rHGH) is not predictable, based on either the parameters known to affect the response to treatment or the type of defect in the GH-insulin-like growth factor (IGF-1) axis. The wide variation in growth velocity observed during rHGH treatment suggests that treatment with the usual dose of rHGH (0.6 U/kg/week) cannot be considered effective in all patients, although rHGH has been successful in some patients. Therefore further studies are required in order to evaluate the effects of supraphysiological doses of rHGH on growth. Since these patients are prone to develop abnormal glucose homeostasis, oral glucose tolerance tests must be performed periodically during rHGH treatment.
 ...
PMID:Clinical experience with growth hormone treatment in patients with beta-thalassaemia major. 1803 Nov 17

Growth failure is one of the most common problems in children with thalassemia with multiple etiologies. We present a case of celiac disease, an underdiagnosed cause of growth failure in a child with beta-thalassemia major. A 10-year-old boy on a hypertransfusion regimen was referred for early onset growth failure. Serology for hepatitis B, hepatitis C, and HIV was negative. Serum zinc levels were normal. Thyroid function tests and growth hormone secretion, evaluated with clonidine stimulation test were normal. Malabsorption syndrome was suspected, even in the absence of gastrointestinal symptoms. Tissue transglutaminase were highly raised >300 IU/mL (normal values <15 U/L). Characteristic mucosal lesions on jejunal biopsy confirmed the diagnosis of celiac disease. Institution of a gluten-free diet resulted in rapid gain in weight and improvement in height velocity.
 ...
PMID:Celiac disease in a child with beta-thalassemia major: a need for improved screening and awareness. 1913 78

Osteopenia and osteoporosis cause severe problems in thalassemic patients. The pathogenesis of bone loss in thalassemia is multifactorial. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the accelerated hemopoiesis with progressive marrow expansion, the direct iron toxicity on osteoblasts, the iron chelators, the deficiency of growth hormone or insulin growth factors, all have been identified as major causes of osteoporosis in thalassemia. However, despite the normalization of hemoglobin levels, adequate hormone replacement and effective iron chelation, patients continue to show an unbalanced bone turnover with an increased resorptive phase resulting in seriously diminished bone mineral density (BMD). During the last decade bisphosphonates have been used for the management of osteoporosis in thalassemia. Alendronate, pamidronate and zoledronic acid have shown efficacy in increasing BMD in thalassemic patients. However, further trials must be conducted in order to clarify the exact role of each bisphosphonate, the long-term benefit and side-effects as well as the effects of the combination of bisphosphonates with other effective agents, such as hormonal replacement, on thalassemia osteoporosis.
 ...
PMID:Pathogenesis and management of osteoporosis in thalassemia. 1933 61

The aim was to study the prevalence and severity of hormonal imbalance affecting growth, gonadal and thyroid function in thalassaemic patients and to find out whether any correlation exists between the degree of tissue iron-overload and several patients characteristics like age, gender, foetal haemoglobin (HbF) level, type of thalassaemia (beta or E-beta), and the presence of specific endocrine abnormality. Sixty-eight consecutive non-chelated, transfusion-dependent patients of beta and E-beta-thalassaemia with significant tissue iron overload (serum ferritin more than 2000 microg/l) were included. Standing height was noted and clinical features of hypogonadism were recorded. Insulin tolerance test was done to assess growth hormone reserve. Serum oestradiol, T3,T4,TSH were measured in fasting clotted sample, while pooled sera (from 3 consevutive morning samples) was used for testosterone, FSH and LH. Hypogonadism was the commonest abnormality, both in males (52.28%) and females (35.89%) followed by growth retardation (20.58%) and reduced growth hormone reserve (7.35%). There was no significant difference in the prevalence of endocrine dysfunction with regard to patient's age, gender, type of thalassaemia (beta or E-beta) amd HbF level. Hypogonadic females had a significantly elevated mean serum ferritin level. Subclinical hypothyroidism was present in 23.52% of patients, related to the duration of disease. No association was found between pituitarty and thyroid dysfunction.
 ...
PMID:A study on endocrine dysfunction in thalassaemia. 1955 99


<< Previous 1 2 3 4 Next >>